Since their return from the Persian Gulf region, a large number of veterans have reported health problems. Among the most frequent complaints are fatigue, muscle pain, and muscle weakness. In an effort to investigate the etiology responsible for the ongoing chronic fatigue and muscle weakness, we are performing a comprehensive evaluation of skeletal muscle in PG veterans afflicted with chronic fatigue and muscular weakness and in a control group of healthy veterans. To date, 40 Persian Gulf Veterans have been studied 25 suffering from chronic fatigue and muscle weakness (age 33$3yrs; weight 181$11lbs) and 15 controls (age 28$2yrs; weight 180$6lbs). There was only an 8% difference in the rate of PCr resynthesis, a measure of in vivo oxidative capacity, between the veterans with muscular complaints and the healthy veterans. The PCr resynthesis rate constant was 2.19$0.10 s-1 (Mean$SEM) in the sick Persian Gulf veterans and 2.36$0.11 s-1 in the healthy control veterans. Additionally, MRI measurements of subjects from both populations revealed no difference in the cross-sectional area of the calf muscles. Resting spectra from both populations showed little difference. The Pi/PCr of the healthy veterans was 0.13$0.01 [mM] compared with 0.14$0.01 [mM] in sick veterans. In order to verify the subjective reports of muscle weakness and fatigue, we measured muscular strength and endurance in both populations. The right calf was monitored during isometric and isokinetic contractions. Isometric strength differed between the populations by 50%, with an average peak torque of 86.6$10.8 in the sick veterans and 128.7$11.3 in the healthy ve terans. The relative fatiguability, in contrast, was the same in both groups. However, the sick group performed half as much total absolute work during the same number of maximal contractions (412.1$74.6J versus 795.1$124.3J for the healthy group).Further examination of skeletal muscle using a combination of electrical stimulation, muscle biopsies and EMG will be performed to confirm the myopathic origin of chronic fatigue and muscle weakness in PG illness. In addition, DNA samples will be screened for genetic defects, or polymorphisms, which may have predisposed individuals to develop Persian Gulf illness.